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Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance.

AIMS: Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. METHODS: After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas-liquid chromatography/mass spectrometry. RESULTS: Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) microV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6)microV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (rs = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) microV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4,076 (1091) vs. 5,219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. CONCLUSIONS: Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density).

Diabetes Mellitus, Type 1↗

Natural genetic variation of freezing tolerance in Arabidopsis.

Low temperature is a primary determinant of plant growth and survival. Using accessions of Arabidopsis (Arabidopsis thaliana) originating from Scandinavia to the Cape Verde Islands, we show that freezing tolerance of natural accessions correlates with habitat winter temperatures, identifying low temperature as an important selective pressure for Arabidopsis. Combined metabolite and transcript profiling show that during cold exposure, global changes of transcripts, but not of metabolites, correlate with the ability of Arabidopsis to cold acclimate. There are, however, metabolites and transcripts, including several transcription factors, that correlate with freezing tolerance, indicating regulatory pathways that may be of primary importance for this trait. These data identify that enhanced freezing tolerance is associated with the down-regulation of photosynthesis and hormonal responses and the induction of flavonoid metabolism, provide evidence for naturally increased nonacclimated freezing tolerance due to the constitutive activation of the C-repeat binding factors pathway, and identify candidate transcriptional regulators that correlate with freezing tolerance.

Acclimatization↗

Effects of attentional direction, age, and coping style on cold-pressor pain in children.

This study assessed the relative efficacy of two imagery-based attentional strategies for modifying pain experience in children. Children aged 7-14 years (n = 120) were randomly assigned to one of three conditions: distraction, sensory-focussing or control (no imagery). The distraction condition prompted children to focus their attention externally; the sensory-focussing condition prompted the child to focus internally on physical sensations. Self-report measures of pain coping style preferences and imagery ability were completed. Children's pain tolerance and perceptions of pain intensity were assessed using a 10 degrees C cold-pressor task. Results showed pain intensity ratings after 1 min were lower for both intervention conditions than for the controls. Younger children (7-9 years) showed higher pain tolerance in the distraction condition than in the sensory-focussing condition, whereas both interventions were equally effective for older children (10-14 years). Among older children, coping style interacted with the intervention type: in the sensory-focussing condition, pain tolerance was negatively associated with self-reported distraction-based coping style, whereas in the distraction condition this association was positive. The results are interpreted with reference to current models of attention. The implications for use of attentional strategies in helping children to cope with clinical pain are discussed.

Adaptation, Psychological↗

Abscisic Acid-induced freezing resistance in cultured plant cells.

The effect of abscisic acid (ABA) on the cold hardiness of cell suspension was investigated. Cell suspension cultures of winter wheat (Triticum aestivum L. cv Norstar), winter rye (Secale cereale L. cv Cougar), and bromegrass Bromo inermis Leyss treated with 7.5 x 10(-5) molar ABA for 4 days at 20 degrees C could tolerate -30 degrees C, whereas the control cultures tolerated only -7 to -8 degrees C. The optimum concentration for increasing the cold hardiness of the cultures was 7.5 x 10(-5) molar. The degree of cold hardiness and the rate of hardening obtained by ABA treatment was significantly higher than that induced by low temperature alone. Of ten species tested, ABA was only effective on those cultures which were capable of cold hardening upon exposure to low temperatures. The results suggest that ABA bypasses the cold requirement for hardening and also suggests that ABA triggers the genetic system(s) responsible for inducing the hardening process.

Journal Article↗

Uric acid and glutathione levels during short-term whole body cold exposure.

Ten healthy subjects who swim regularly in ice-cold water during the winter (winter swimming), were evaluated before and after this short-term whole body exposure. A drastic decrease in plasma uric acid concentration was observed during and following the exposure to the cold stimulus. We hypothesize that the uric acid decrease can be caused by its consumption after formation of oxygen radicals. In addition, the erythrocytic level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione also increased following cold exposure, which supports this hypothesis. Furthermore, the baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of nonwinter swimmers. This can be viewed as an adaptation to repeated oxidative stress, and is postulated as mechanism for body hardening. Hardening is the exposure to a natural, e.g., thermal stimulus, resulting in an increased tolerance to stress, e.g., diseases. Exposure to repeated intensive short-term cold stimuli is often applied in hydrotherapy, which is used in physical medicine for hardening.

Acclimatization↗

[Diurnal differences in the effectiveness of an analgesic].

At different times of the day, the effect of an analgesic was systematically tested on healthy teeth by using a cold stimulus. The measure of the analgetic effect was the alteration of pain threshold measured by means of the minimum cold application time. In addition to the already known spontaneous variations in pain tolerance at the various times of the day, it was found that in the evening the effect of an analgesic is reduced and begins more slowly.

Adult↗

Relationship between pain sensitivity, cardiovascular reactivity to cold pressor test and indexes of activity of the adrenergic and opioid system.

An association between increased blood pressure levels and hypoalgesia has been reported in the experimental animal and in man. The relation between pain perception and cardiovascular function is however still obscure. In order to gain some insight into this aspect, normotensive subjects with low and high tolerance to pain, as assessed by tooth pulp stimulation, were compared for blood pressure and heart rate during cold pressor test, 24 hr urinary catecholamines, supine and upright PRA and plasma beta-endorphin levels. No significant difference was observed between the two groups for casual blood pressure, heart rate and PRA. Compared to subjects with low tolerance to pain, those with high tolerance to pain were significantly older and had: 1) significantly higher levels of diastolic blood pressure and of beta endorphin levels during cold pressor test; 2) significantly higher beta-endorphin levels after cold pressor test; 3) a significantly higher excretion of noradrenaline (but not of adrenaline and dopamine).

Adult↗

Anoxia tolerance in turtles: metabolic regulation and gene expression.

Freshwater turtles of the Trachemys and Chrysemys genera are champion facultative anaerobes able to survive for several months without oxygen during winter hibernation in cold water. They have been widely used as models to identify and understand the molecular mechanisms of natural anoxia tolerance and the molecular basis of the hypoxic/ischemic injuries that occur in oxygen-sensitive systems and underlie medical problems such as heart attack and stroke. Peter L. Lutz spent much of his career investigating turtle anaerobiosis with a particular focus on the mechanisms of brain ion homeostasis and neurotransmitter responses to anoxia exposure and the mechanisms that suppress brain ion channel function and neuronal excitability during anaerobiosis. Our interests intersected over the mechanisms of metabolic rate depression which is key to long term anoxia survival. Studies in my lab have shown that a key mechanism of metabolic arrest is reversible protein phosphorylation which provides coordinated suppression of the rates of multiple ATP-producing, ATP-utilizing and related cellular processes to allow organisms to enter a stable hypometabolic state. Anoxia tolerance is also supported by selective gene expression as revealed by recent studies using cDNA library and DNA array screening. New studies with both adult T. scripta elegans and hatchling C. picta marginata have identified prominent groups of genes that are up-regulated under anoxia in turtle organs, in several cases suggesting aspects of cell function and metabolic regulation that have not previously been associated with anaerobiosis. These groups of anoxia-responsive genes include mitochondrially-encoded subunits of electron transport chain proteins, iron storage proteins, antioxidant enzymes, serine protease inhibitors, transmembrane solute carriers, neurotransmitter receptors and transporters, and shock proteins.

Adaptation, Physiological↗

The impact of threatening information about pain on coping and pain tolerance.

This study examined the impact of threatening information on coping and pain tolerance in a healthy adult sample. Prior to engaging in a Cold Pressor Test (CPT), 121 college students were randomly assigned to one of three conditions: a threat condition in which they read an orienting passage warning them about symptoms and consequences of frostbite (pain as a signal for nociception), a reassurance condition in which they read an orienting passage about the safety of the CPT (pain independent of nociception), or a control condition in which no orienting passage was read before the experimental task. Only 15.6% of participants in the threat group completed the CPT to its 4-minute duration, compared with 55.6% in the reassurance group and 45.2% of those in the control group. Even though groups did not differ on level of reported pain, threatened participants catastrophized more about the pain and reported less use of cognitive coping strategies (reinterpreting pain sensations, ignoring pain, diverting attention away from pain to other experiences, and using coping self-statements) than other respondents. A path analysis indicated that the relation between threat and pain tolerance was fully mediated by catastrophizing and cognitive coping. Together, findings suggest that pain appraised as threatening contributes to a specific pattern of coping responses associated with a reduced capacity to bear pain.

Adaptation, Psychological↗

Adult diapause and cold hardiness in Aulacophora nigripennis (Coleoptera: Chrysomelidae).

We investigated the control of diapause termination and seasonal changes of cold hardiness and polyol content in Aulacophora nigripennis. Adults were ready to start post-diapause development upon transfer to high temperature by late February irrespective of photoperiod. Photoperiod probably functions to maintain diapause before winter because adults resume reproductive development at a long photoperiod in autumn. Adults showed a decreased supercooling point (SCP), increased chill tolerance and high myo-inositol content during winter. Chill tolerance at 0 degrees C appears to be a more suitable indicator of their cold hardiness than SCP because they die at 0 degrees C without freezing and they normally have no chance of being exposed to low subzero temperatures close to their SCP. The temporal pattern for changes in chill tolerance was synchronized with that for fluctuations in myo-inositol content, indicating a possible causal relationship between the two phenomena.

Journal Article↗

Cold hardiness abilities vary with the size of the land snail Cornu aspersum.

The land snail Cornu aspersum (syn. Helix aspersa) living in Brittany (France) can be considered partially freezing tolerant as it possesses a low ability to supercool and a limited capacity to bear freezing of its body tissues. The absence of a marked cold hardiness strategy permits the emphasis of the role of parameters such as individual size or water mass (W(M)) contained by the organism. Adult snails (shell diameter 30-32 mm) had a supercooling ability, about 1-1.5 degrees C lower than that of immatures (shell diameter 12-20 mm) and survived longer to an exposure to -5 degrees C, with an Lt(50) comprised between 6.0 and 9.8 h against 2.6 to 4.2 h for immature snails. This better ability to bear freezing was explained by the faster dynamic of body ice formation observed in small individuals, which attained ice lethal quantity more rapidly. At the species level, large snails will then tend to be more tolerant to freezing and small ones to be freezing avoidant, a statement also observable at the phylum level.

Acclimatization↗

Entering diapause is a prerequisite for successful cold-acclimation in adult Graphosoma lineatum (Heteroptera: Pentatomidae).

In diapause adults of Graphosoma lineatum overwintering in a field-cage, high chill-tolerance (CT) developed gradually, within 5 months from August to December. In laboratory-acclimation experiments, the diapause state appeared to be an essential pre-condition for successful cold-acclimation and overwintering. First, diapause prevented elevation of the median supercooling point (SCP) by about 5.5 degrees C that accompanies the onset of reproductive activity in non-diapause specimens. Second, diapause allowed subsequent physiological changes resulting in cold-acclimation during a gradual (18-day) decrease of temperature from 25 to 0 degrees C. No, or very modest, cold-acclimation was observed in non-diapause specimens. Decrease of temperature led to a rapid loss of ca. 1/3 of the body water in both non-diapause and diapause specimens. Approximately 0.1 M of trehalose accumulated in tissues of diapause specimens only, and haemolymph osmolality rose from 347 mOsm (at 25 degrees C) to 444 mOsm after an 18-day cold-acclimation and to 764 mOsm during further storage at 0 degrees C for 100 days. Upon transfer of cold-acclimated diapause specimens back to 25 degrees C for one week (de-acclimation), the high CT was lost, the SCP elevated by about 2.5-3 degrees C, and the levels of trehalose, water content and haemolymph osmolality returned to pre-acclimation or non-diapause levels.

Journal Article↗

Importance of generalized defective perception of painful stimuli as a cause of silent myocardial ischemia in chronic stable angina pectoris.

Growing evidence indicates that most patients with coronary artery disease frequently have episodes of painless myocardial ischemia. Previous studies from our institution show that the severity and duration of myocardial ischemia are necessary but not sufficient factors to explain the occurrence of anginal pain. The responses to a battery of painful stimuli were studied in 12 patients with predominantly painless (group A) and in 15 patients with predominantly painful (group B) ischemic episodes. The severity of myocardial ischemia as assessed by the measurement of ST-segment depression during exercise stress testing and during ambulatory electrocardiographic monitoring was comparable in the 2 groups. Patients in group A had a significantly higher threshold and tolerance for forearm ischemia (+32%, p less than 0.05; +120%, p less than 0.001), cold (+100%, p less than 0.05; +180%, p less than 0.01) and electrical skin stimulation (+145%, p less than 0.01; +109%, p less than 0.01), but the overlap between the 2 groups was often appreciable. In the 6 patients with the longest tolerance times for forearm ischemic pain (all in group A) and in the 5 having the shortest tolerance times (all in group B), plasma levels of beta endorphin, met-enkephalin, noradrenaline and adrenaline were similar during both the basal state and the induction of forearm ischemic pain. Thus, a generalized defective perception of painful stimuli plays an important role in many patients with predominantly painless myocardial ischemia. Other mechanisms, however, may also be important, particularly in patients whose threshold and tolerance values overlap with those of patients who have predominantly painful myocardial ischemia.

Angina Pectoris↗

Insulin resistance in the aged: the role of the peripheral insulin receptors.

In the healthy subject, glucose tolerance tends to decrease with age due to impaired insulin secretion and/or decreased peripheral insulin activity. An oral glucose (100 g) tolerance test was performed on 12 aged (70 +/- 4 yr) and 8 young (32 +/- 7 yr) subjects; these subjects underwent laparatomy for cholecystectomy or the management of abdominal diseases. Subcutaneous adipose tissue was removed during surgery and fat cells, prepared according to a personal modification of Rodbell's method, were incubated in a medium containing monoiodo- and cold insulin to evaluate insulin binding and affinity constants. The results of the tolerance test pointed to an insulin resistant state i.e., impaired glucose tolerance coupled with normal plasma insulin, as previously shown also by us using other methods in the aged subject. The binding study demonstrates a distinct insulin receptor decrease in fat cells from the older subjects (185,000 +/- 19,200 as opposed to 310,000 +/- 12,000), without any change in affinity constants. The result indicates that insulin resistance in the aged may be attributed at least in part to a reduction in the number of insulin receptors on the target cells. This could be a consequence of aging itself, as proposed by other workers in the case of old fat rats.

Adipose Tissue↗

Effect of age and long-term stress experience on adaptation to stress analgesia in mature rats: role of opioids.

The effects of aging and previous long-term stress on development of tolerance to stress-induced analgesia were evaluated in male Sprague-Dawley rats exposed to intermittent cold water swims (ICWS) in 2 degrees C water (eighteen 10-s exposure, three/min) on 15 consecutive days. Analgesia was measured by the tail-flick test prior to and 30 min after ICWS. In young rats (4 months), tolerance developed faster and asymptotic tolerance was acquired sooner and was more complete than in older rats (15-16 months). Previous long-term exposure (but not the age at which it occurred) accelerated the development and acquisition of asymptotic tolerance to reexposure. Naltrexone (10 mg/kg, ip) partially and completely reversed tolerance to ICWS analgesia in 4- and 9-10-month-old rats, respectively, results suggesting that the opioids are involved in ICWS-analgesia tolerance in both young and old mature rats. In young animals, a second mechanism, naltrexone-insensitive, may be responsible for at least some of the differences in ICWS tolerance found between young and old mature adult rats.

Aging↗

Purification, characterization and cDNA cloning of the 200 kDa protein induced by cold acclimation in wheat.

We have purified to homogeneity the 200 kDa protein induced specifically by low temperature in wheat (Triticum aestivum L.). The boiling solubility of the protein has been used as a main step in the purification procedure. Amino acid composition indicates that the 200 kDa has a compositional bias for glycine (11.4%), threonine (13.3%), and alanine (22.0%). Using oligonucleotide probes, we have isolated a clone (p Wcs200) from a cold-acclimated winter wheat cDNA library. Northern analysis demonstrated that the expression of the corresponding gene was specifically upregulated by low temperature. Southern analysis showed that the gene organization and the relative copy number were identical in two cultivars differing in their capacity to develop freezing tolerance. Protein sequence and immunological analyses indicate that this protein shares similar features with the 50 kDa protein induced during cold acclimation of wheat. The two proteins are boiling-soluble, and possess similar repeated elements. These elements may be important for the development of freezing tolerance. We have shown that the 200 kDa protein is the largest member of a family of immunologically-related cold-induced proteins in wheat. Expression of pWcs200 in E. coli yielded a product of around 200 kDa, indicating that the clone contains most of the coding region for this protein.

Acclimatization↗

Inorganic ions in cold-hardiness.

Cold exposure and freezing may affect ion distribution in several ways and reduce physiologically important ionic gradients. Both freeze-avoiding and freeze-tolerant organisms have developed mechanisms to handle this stress. Supercooled insects seem to be able to maintain their ionic gradients even at temperatures far below zero. When freeze-tolerant insects freeze, ions diffuse down their concentration gradients across the cell membranes and reach electrochemical equilibrium. They quickly reverse this transmembrane diffusion when they are thawed. Trace metals may affect mechanisms for cold-hardening in different ways and reduce cold-hardiness. Freezing may give rise to toxic concentrations of metal ions, and freeze-tolerant organisms probably need to inactivate toxic trace metals. Ice nucleating agents may be important in this context.

Acclimatization↗